国際静脈物流システムの設計に関する研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学准教授 村上 進亮, 東京大学教授 藤田 豊久, 東京大学教授 青山 和浩, 東京大学特任准教授 田中 謙司, 東京大学特任准教授 醍醐 市朗University of Tokyo(東京大学

The Stretcher Operation of KSR (NUCLEAR SCIENCE RESEARCH FACILITY-Particle and Photon Beams)

The electron ring KSR has been utilized as a pulse stretcher of the 100 MeV S-band electron linac. The duty factor of the electron beam has been increased drastically more than 90% from 2 10-5

Glucotoxicity Induces Insulin Promoter DNA Methylation in Beta Cells

Recent studies have implicated epigenetics in the pathophysiology of diabetes. Furthermore, DNA methylation, which irreversibly deactivates gene transcription, of the insulin promoter, particularly the cAMP response element, is increased in diabetes patients. However, the underlying mechanism remains unclear. We aimed to investigate insulin promoter DNA methylation in an over-nutrition state. INS-1 cells, the rat pancreatic beta cell line, were cultured under normal-culture-glucose (11.2 mmol/l) or experimental-high-glucose (22.4 mmol/l) conditions for 14 days, with or without 0.4 mmol/l palmitate. DNA methylation of the rat insulin 1 gene (Ins1) promoter was investigated using bisulfite sequencing and pyrosequencing analysis. Experimental-high-glucose conditions significantly suppressed insulin mRNA and increased DNA methylation at all five CpG sites within the Ins1 promoter, including the cAMP response element, in a time-dependent and glucose concentration-dependent manner. DNA methylation under experimental-high-glucose conditions was unique to the Ins1 promoter; however, palmitate did not affect DNA methylation. Artificial methylation of Ins1 promoter significantly suppressed promoter-driven luciferase activity, and a DNA methylation inhibitor significantly improved insulin mRNA suppression by experimental-high-glucose conditions. Experimental-high-glucose conditions significantly increased DNA methyltransferase activity and decreased ten-eleven-translocation methylcytosine dioxygenase activity. Oxidative stress and endoplasmic reticulum stress did not affect DNA methylation of the Ins1 promoter. High glucose but not palmitate increased ectopic triacylglycerol accumulation parallel to DNA methylation. Metformin upregulated insulin gene expression and suppressed DNA methylation and ectopic triacylglycerol accumulation. Finally, DNA methylation of the Ins1 promoter increased in isolated islets from Zucker diabetic fatty rats. This study helps to clarify the effect of an over-nutrition state on DNA methylation of the Ins1 promoter in pancreatic beta cells. It provides new insights into the irreversible pathophysiology of diabetes

Hyponatremia-Induced Osteoporosis

There is a high prevalence of chronic hyponatremia in the elderly, frequently owing to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Recent reports have shown that even mild hyponatremia is associated with impaired gait stability and increased falls. An increased risk of falls among elderly hyponatremic patients represents a risk factor for fractures, which would be further amplified if hyponatremia also contributed metabolically to bone loss. To evaluate this possibility, we studied a rat model of SIADH and analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III). In rats, dual-energy X-ray absorptiometry (DXA) analysis of excised femurs established that hyponatremia for 3 months significantly reduced bone mineral density by approximately 30% compared with normonatremic control rats. Moreover, micro-computed tomography (µCT) and histomorphometric analyses indicated that hyponatremia markedly reduced both trabecular and cortical bone via increased bone resorption and decreased bone formation. Analysis of data from adults in NHANES III by linear regression models showed that mild hyponatremia is associated with increased odds of osteoporosis (T-score –2.5 or less) at the hip [odds ratio (OR) = 2.85; 95% confidence interval (CI) 1.03–7.86; p < .01]; all models were adjusted for age, sex, race, body mass index (BMI), physical activity, history of diuretic use, history of smoking, and serum 25-hydroxyvitamin D [25(OH)D] levels. Our results represent the first demonstration that chronic hyponatremia causes a substantial reduction of bone mass. Cross-sectional human data showing that hyponatremia is associated with significantly increased odds of osteoporosis are consistent with the experimental data in rodents. Our combined results suggest that bone quality should be assessed in all patients with chronic hyponatremia. © 2010 American Society for Bone and Mineral Research

Beam and SKS spectrometers at the K1.8 beam line

High-resolution spectrometers for both incident beams and scattered particles have been constructed at the K1.8 beam line of the Hadron Experimental Facility at J-PARC. A point-to-point optics is realized between the entrance and exit of QQDQQ magnets for the beam spectrometer. Fine-pitch wire chamber trackers and hodoscope counters are installed in the beam spectrometer to accept a high rate beam up to 107 Hz. The superconducting kaon spectrometer for scattered particles was transferred from KEK with modifications to the cryogenic system and detectors. A missing-mass resolution of 1.9 ± 0.1 MeV/c2 (FWHM) was achieved for the ∑ peaks of (π±, K+) reactions on a proton target in the first physics run of E19 in 2010

Possibility of Sustainable Entry into Overseas Port Operation Markets by Japanese Companies

The Japanese government has set an overseas infrastructure deployment policy to involve Japanese companies in all upstream to downstream processes, that is, from project formation, procurement, and construction to operation and maintenance. Although Japanese companies have been hitherto involved in overseas port development through Official Development Assistance, their entry into overseas port operation projects has been limited, meaning the realization of the policy is not expected to be easy. This study thus examines the possibility of sustainable entry into overseas port operation markets by Japanese companies. Specifically, we review port governance in Japan, characteristics of the Japanese market in the global market, and the status of the participation of domestic terminal operators in Japan and overseas, and then identify the possibilities and methods of sustainable inclusion in the future overseas port operations by interviewing representative companies and the government. We finally provide future directions in terms of both increasing entry opportunities and improving the entry environment

Possibility of Sustainable Entry into Overseas Port Operation Markets by Japanese Companies

The Japanese government has set an overseas infrastructure deployment policy to involve Japanese companies in all upstream to downstream processes, that is, from project formation, procurement, and construction to operation and maintenance. Although Japanese companies have been hitherto involved in overseas port development through Official Development Assistance, their entry into overseas port operation projects has been limited, meaning the realization of the policy is not expected to be easy. This study thus examines the possibility of sustainable entry into overseas port operation markets by Japanese companies. Specifically, we review port governance in Japan, characteristics of the Japanese market in the global market, and the status of the participation of domestic terminal operators in Japan and overseas, and then identify the possibilities and methods of sustainable inclusion in the future overseas port operations by interviewing representative companies and the government. We finally provide future directions in terms of both increasing entry opportunities and improving the entry environment

Commissioning of the Electron Ring, KSR (NUCLEAR SCIENCE RESEARCH FACILITY?Beams and Fundamental Reaction)

KSR (Kaken Storage Ring) is a compact electron ring in Kyoto University. The circumference of KSR is 25.7 m and the maximum beam energy is 300 MeV. It is designed for the synchrotron light source and the electron pulse stretcher ring. The beam commissioning of KSR had started in September, 1999. In last October, the beam current of 3 mA was stored successfully. The beam parameter measurements and the machine parameter adjustments were carried out. At the end of 1999, the beam current is 10 mA. The typical beam lifetime is 1000 second

Electron Storage and Stretcher Ring, KSR (NUCLEAR SCIENCE RESEARCH FACILITY-Particle and Photon Beams)

An electron storage ring with the maximum energy of 300 MeV and critical wavelength from the dipole section of the 17 nm is under construction. It will also improve the duty factor of the electron beam with the energy of ~100 MeV attaining the average number of 1012 electrons per second with the fairly lower peak current of 0.3 mA, which is suitable for counter experiments